title: The carbohydrate switch between pathogenic and immunosuppressive antigen-specific antibodies.
abstract: IgG antibodies have one conserved N-glycosylation site at Asn 297 in each of their constant heavy chain regions. These Fc glycans influence the overall structure and pro- or anti-inflammatory effector functions of IgG antibodies. The biantennary core glycan structure, consisting of four N-acetyl-glucosamine (GlcNAc) and three mannose residues, can be further decorated with fucose, a bisecting GlcNAc and terminal galactose or galactose plus sialic acid. Non-galactosylated (agalactosylated; G0) IgG antibodies have long been associated with pro-inflammatory effector functions in autoimmune patients with rheumatoid arthritis (RA). In contrast, it has been shown that sialylated IgGs are responsible for anti-inflammatory effects of intravenous immunoglobulin (IVIG; purified IgG from pooled human plasma), which is administered at high doses (2 g/kg) for the systemic treatment of autoimmune patients. It has become increasingly evident that pro-inflammatory immune responses, such as autoimmune reactions, primarily induce antigen-specific G0 IgGs, whereas tolerance induces immunosuppressive galactosylated and sialylated IgGs. Under physiological conditions, differentially glycosylated IgGs mediate their pro- or anti-inflammatory effector functions obviously as immune complexes (IC) in an antigen-specific manner. Therefore, antigen-specific galactosylated and sialylated IgGs may be a promising therapeutic tool for re-establishing tolerance against defined (self-) antigens in autoimmune or allergic patients. Here, we summarize these findings and outline our viewpoint on the development and function of differentially glycosylated antigen-specific IgG antibodies.
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Collin
authors.forename: Marc
authors.initials: M
authors.lastname: Ehlers
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000737:chemistry; D001327:Autoimmune Diseases / Q000628:therapy; D015551:Autoimmunity; D002241:Carbohydrates / Q000737:chemistry*; D005690:Galactose / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000737:chemistry; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000737:chemistry*; D007249:Inflammation; D008358:Mannose / Q000737:chemistry; D051379:Mice; D012794:Sialic Acids / Q000737:chemistry; D018417:Th1 Cells / Q000166:cytology; D058504:Th17 Cells / Q000166:cytology
chemical_list: D000906:Antibodies; D000941:Antigens; D001323:Autoantibodies; D002241:Carbohydrates; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D012794:Sialic Acids; D008358:Mannose; D005690:Galactose
keywords: B-Lymphocytes; IgG; autoimmunity; glycosylation; self-tolerance